Inclisiran, sold under the brand name Leqvio, is a medication used for the treatment of high LDL-C and for the treatment of people with atherosclerotic cardiovascular disease (ASCVD) risk-equivalents, and heterozygous familial hypercholesterolemia.
The data comes from the phase 3 trial ORION-8, an extension of four preceding it.
The data demonstrated that after an initial dose and another at three months, patients with atherosclerotic cardiovascular disease (ASCVD), increased risk of ASCVD or heterozygous familial hypercholesterolemia (HeFH) benefited from consistent lower cholesterol.
The results were presented in a late-breaking session at the European Society of Cardiology (ESC) Congress 2023 in Amsterdam.
Novartis says that ORION-8, the largest clinical trial completed to date with inclisiran, continues to support the consistent long-term efficacy, safety profile, and tolerability of inclisiran, with a total exposure of more than 8,500 patient-years during the trial’s three-year follow-up.
Patients from four previous completed Novartis trials (ORION-9, ORION-10, ORION-11 and ORION-3) received inclisiran every six months for up to an additional three years. It revealed that 78% of patients reached their pre-specified LDL-C targets and on average, LDL-C levels were reduced by approximately 49%. These results demonstrate consistent efficacy as they are comparable to the LDL-C reductions observed at the end of the initial trials.
In addition, the long-term safety data was consistent with previous findings, confirming the well-established safety profile of inclisiran.
Kausik Ray, is professor of public health at Imperial College London and honorary consultant cardiologist at the Imperial College NHS Trust.
He said: “The present findings from the ORION-8 trial reconfirm and extend prior observations about the safety profile and efficacy of inclisiran for people with atherosclerotic cardiovascular disease and those at risk of cardiovascular disease, in whom cholesterol levels are not adequately controlled.
He said that in the largest study presented to date with several thousand injections, he could confirm that twice yearly dosing with the first in class siRNA therapy provides sustained reductions in LDL cholesterol by approximately 49% beyond 6 years of observation.
Ray added: “The safety profile demonstrates no new additional concerns raised during this extended period of follow up. As the senior author in this trial and lead in the ORION development programme as well as an active clinician, I am acutely aware of the unmet clinical need in our patients but also the assurance needed by the clinical community for any novel therapy.
“Therefore, these findings are particularly important in providing clinicians and patients with further assurance helping reduce the gap between guideline recommended care and their implementation.”
Novartis said ORION-8 is part of VictORION, a large dynamic clinical trial program co-created with healthcare partners worldwide to generate evidence on the impact of cholesterol-lowering with inclisiran. The program is enrolling over 60,000 patients, across more than 50 countries and more than 30 clinical trials.
Gerrit Zijlstra, Novartis country medical head and chief medical officer, Novartis UK said: “These results reaffirm our partnership-based approach with the NHS on the basis that administration through primary care could positively impact population health in the UK.
“This will help us to deliver our shared vision for the benefit of UK patients and contribute to reducing the considerable impact of CVD on the population.”
